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482 Background: Population-based studies evaluating outcomes exclusively for metastatic upper tract urothelial carcinoma (mUTUC) are sparse and often only capture patients with de novo (synchronous) metastases as opposed to those who progress to metastatic disease (metachronous). We sought to evaluate the outcomes and costs associated with mUTUC and employ a novel methodology to identify both synchronous and metachronous mUTUC patients using claims data. Additionally, we created a guideline-based quality score to improve quality of care in this space. Methods: Using the SEER-Medicare database we identified patients aged 66 years and older diagnosed with mUTUC between 2004 and 2012. Achievement of the following quality criteria was assessed: 1) cancer-specific survival greater than 12 months; 2) receipt of systemic therapy; 3) receipt of hospice/palliative care. Kaplan-Meier survival curves and Cox proportional hazard models were used to compare overall survival between quality scores (0 vs. ≥1) and synchronous vs. metachronous mUTUC. Total healthcare and Medicare Part D out-of-pocket costs within two years of diagnosis were evaluated. Regression analyses were performed to assess characteristics associated with quality criteria and total healthcare costs. Results: Of the 1,223 patients identified, 381 (31.2%) and 842 (68.8%) had synchronous and metachronous mUTUC, respectively. At least one quality criterion was met in 40.2% of patients. Notably, only 54 patients (4.4%) received palliative care services. On multivariable analysis, patients with synchronous mUTUC (OR:0.55, 95%CI:0.41–0.72), and at least 3 comorbidities (OR:0.68, 95%CI:0.47–0.98), were less likely to achieve at least one quality criterion. Patients meeting quality criteria had longer survival compared with patients who did not meet criteria (HR:0.52, 95%CI: 0.46–0.59). Meeting at least one quality criterion was independently associated with increased costs ($94,677, 95%CI: 87702–101652 vs. $63575, 95%CI: 59598–67552) on multivariable regression analysis. Conclusions: Less than half of mUTUC patients met at least one quality criterion. Quality score achievement was associated with longer overall survival at a modest increase in total healthcare spending. These findings not only provide guidance for future study of rare diseases using secondary data, but also highlight inadequacies in the current management of mUTUC.

461 Background: Prior studies suggest that white light cystoscopy (WLC) alone can fail to detect cases of non-muscle invasive bladder cancer (NMIBC) compared to blue light cystoscopy (BLC). We describe bladder cancer outcomes and the impact of BLC among NMIBC patients in an equal access setting. Methods: A total of 378 NMIBC patients within the Veterans Affairs system that had a CPT code for BLC from December 1, 2014 to December 31, 2020 were assessed. We determined recurrence rates and time to recurrence prior to BLC (i.e. after previous WLC if available) and following BLC. We used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, and overall survival. Results: Of 378 patients with complete data, 43 (11%) were Black and 300 (79%) White. Median follow-up was 40.7 months from bladder cancer diagnosis. There were 194 (51%) patients with either TaHG or T1 without CIS; 52 (14%) had CIS with or without TaHG or T1; and 127 (34%) had TaLG only. A total of 239 (63%) patients received BCG at any point during the study. Median time to first recurrence following BLC was longer compared to WLC alone (40 (33-NE) vs. 26 (17-39) months). The risk of recurrence was significantly lower following BLC (Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.54-0.90). There was no significant difference in recurrence (Hazard Ratio (HR) 0.83; 95% Confidence Interval (CI) 0.48-1.43), progression (HR 1.46; 95% CI 0.45-4.74), and overall survival (HR 0.69; 95% CI 0.29-1.65) following BLC by Black vs. White race. Conclusions: In this study from an equal access setting in the VA, we observed significantly decreased risk of recurrence and prolonged time interval to recurrence following BLC compared to WLC alone. There was no difference in any bladder cancer outcomes by race.

455 Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term periods of cost. Our study objective is to compare the 2- and 5-year costs associated with trimodal therapy (TMT) versus radical cystectomy (RC) benchmarked against costs for patients who received no curative treatment. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Medicare expenditures were summed from inpatient, outpatient, and physician services within 2 and 5 years of diagnosis to determine total costs Total Medicare costs at 2-and 5-years following TMT versus RC were compared using inverse probability of treatment-weighted (IPTW) propensity score models. Results: A total of 2,537 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2009. Total median costs for patients that received no definitive/systemic treatments (RC, TMT, radiotherapy alone, or chemotherapy alone) were $73,780 vs. $88,275 at 2-and 5-years respectively. Total median costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, p

527 Background: Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) have heterogeneous outcomes with African Americans (AAs) having worse survival than European Americans (EAs). It is unknown whether race-based biological differences contribute to this disparity. Methods: We performed a retrospective cohort study including patients from the University of Texas Medical Branch (UTMB) and the Durham VA Health Care System (DVAHCS) from 2010-2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions of high-risk NMIBC by race were performed using the UROMOL classification system. Results: A total of 26 patients (14 AAs and 12 EAs) matched on age and sex were included with no significant difference in clinical stage group (CIS +/- T1 or TaHG vs. TaHG or T1, no CIS), smoking status, or progression. We found a similar racial UROMOL subtype distribution with class 2a being most common. A total of 10 genes were discovered to be commonly upregulated differentially expressed genes (up-DEGs) in AAs vs EAs. EFEMP1, which has been associated with progression to muscle-invasive bladder cancer (MIBC) in vitro, and S100A16 gene expression, which has been implicated with mitomycin C resistance in bladder cancer in vitro, was significantly more common among AAs. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which five distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction ability. We mapped the expression of the 10 genes commonly up-DEGs by race as a function of the five malignant subtypes. This showed borderline (p = 0.056) differences among the subtypes suggesting AA and EA patients may be expected to have different therapeutic responses to treatments for BC. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3 bladder tumor cell population. Conclusions: In this small sample, we found similar subtype distribution among high-risk NMIBC patients according to race. However, gene expression differs by race, supporting potential novel race-based etiologies for differences in muscle-invasion, response to treatments, and transcriptome pathway regulations. Further biological studies in NMIBC molecular sub-stratification, associated treatment(s), and prognoses in a larger cohort are needed to support these hypotheses.

447 Background: Mortality from bladder cancer (BC) increases exponentially once it invades the muscle. At the population level, accurate delineation of these patients is challenging. Methods: To develop and validate a natural language processing (NLP) model for automatically identifying muscle-invasive BC (MIBC) patients, aiding in population-based BC research. All patients with a CPT code for transurethral resection of bladder tumor (TURBT) (N = 76,060) were selected from the Department of Veterans Affairs (VA) Corporate Data Warehouse database. A sample of 600 patients (with 2,337 full-text notes) who had TURBT and confirmed pathology results were selected for NLP model development (500 patients) and validation (100 patients). Muscle-invasion (yes/no), unknown, or no cancer, were confirmed by detailed chart review of pathology notes. The NLP performance was assessed by calculating the sensitivity, positive predictive value (PPV), and overall accuracy at the individual note and patient levels. Results: In the validation cohort, the NLP model had overall accuracy of 88% and 92% at the note and patient levels. Specifically, PPV and specificity for predicting muscle-invasion on note level were 83% and 70%, respectively. The model classified non-muscle invasive BC (NMIBC) with 98% sensitivity at both the note and patient levels. Although the sensitivity for MIBC was 70% for note-level determination, the sensitivity was 86% when evaluated at the patient level. When applying the model to 71,200 patients VA-wide, the model classified 13,642 (19%) as having MIBC and 47,595 (66%) as NMIBC. The NLP model was able to identify invasion status for 96% TURBT patients at the population level. Inherent limitations include relatively small training set given the size of the VA population. Conclusions: This NLP model for identifying muscle-invasion at the population level had high accuracy. The NLP model may be a practical and accurate tool for efficiently identifying BC invasion status and may potentially aid in population-based BC research in the VA.

TPS4586 Background: The standard of care for patients with muscle-invasive bladder cancer (MIBC) consists of neoadjuvant chemotherapy and radical cystectomy (RC) or chemoradiotherapy (CRT). However, RC is associated with potential morbidity or mortality from the procedure. TAR-200 is an intravesical drug-delivery system designed for the local continuous release of gemcitabine within the bladder. Cetrelimab is an investigational immunoglobulin G4 anti–programmed cell death protein-1 antibody. In patients with MIBC, this clinical trial will evaluate whether combination treatment with intravesical TAR-200 and systemic cetrelimab will result in enhanced local and systemic antitumor activity versus concurrent CRT. Methods: SunRISe-2 (NCT04658862) is a prospective, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of intravesical TAR-200 plus systemic cetrelimab versus CRT in participants with MIBC. Eligible participants are aged ³18 years with an ECOG performance status of 0, 1, or 2, and histologically proven, cT2-T4a, N0, M0 urothelial carcinoma of the bladder diagnosed within 90 days of the randomization date, and who refuse or are ineligible for RC. Approximately 550 participants will be randomized in a 1:1 ratio and with stratification by 2 factors: transurethral resection of bladder tumor screening results (visibly complete vs incomplete) and screening tumor stage (T0 vs Ta/T1/Tis vs T2-T4a). Participants in Arm 1 will receive intravesical TAR-200 every 3 weeks for the first 18 weeks on study; and, beginning at week 24, every 12 weeks through study year 3. Cetrelimab will be dosed every 3 weeks until month 18. Participants in Arm 2 will receive standard of care CRT (with either cisplatin or gemcitabine, for up to 6 weeks). A primary disease assessment will be performed at week 18 to evaluate treatment response in both arms. Subsequent assessments (axial imaging and cystoscopy) will occur at week 24 and every 12 weeks thereafter through study year 2, and then every 24 weeks through study year 5. The primary endpoint is bladder intact event-free survival. Key secondary endpoints include metastasis-free survival, overall survival, overall response rate (at week 18), and safety and tolerability. Other/exploratory end points include assessments of cancer-specific survival, time to symptomatic progression, pharmacokinetics, immunogenicity, health-related quality of life, healthcare resource utilization, and biomarkers. Participants are being enrolled at approximately 272 study sites worldwide. The study opened for enrollment in December 2020. Clinical trial information: NCT04658862.

419 Background: Multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs in MIBC. However, ICIs remain costly. We conducted a cost-effectiveness analysis comparing neoadjuvant ICIs with CBC. Methods: We applied a decision analytic simulation model with a health care payer perspective and two-year time horizon to compare neoadjuvant ICIs vs CBC. For the primary analysis we compared pembrolizumab with dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC). We performed a secondary analysis with gemcitabine/cisplatin (GC) as CBC and exploratory analyses with atezolizumab or nivolumab/ipilimumab as ICIs (vs both ddMVAC and GC). We input pCR rates from trials (ICIs) or a weighted average of prior studies (CBC) and costs from average sales price. Outcomes of interest included costs, 2-year recurrence-free survival (RFS), and incremental cost-effectiveness ratio (ICER) of cost per 2-year RFS. A threshold analysis estimated a pCR rate or price reduction for ICI to be cost-effective and one-way and probabilistic sensitivity analyses were performed. Results: Results of the cost effectiveness analysis are shown in the table. The incremental cost of pembrolizumab compared with ddMVAC was $8,042 resulting in an incremental improvement of 0.66% in 2-year RFS for an ICER of $1,218,485 per 2-year RFS. A pCR of 71% or a 26% reduction in cost of pembrolizumab would render it more cost-effective with an ICER of $100,000 per 2-year RFS. GC required a 96% pembrolizumab cost reduction to achieve an ICER of $100,000 per 2-year RFS. Atezolizumab appeared to be more cost-effective than ddMVAC, even though the 2yr RFS was 0.66% worse. Conclusions: ICIs were not cost-effective as neoadjuvant therapies, except when atezolizumab was compared with ddMVAC. Pembrolizumab would approach cost-effective thresholds with 26% or 96% reduction in cost when compared to ddMVAC and GC, respectively. Randomized clinical trials, larger sample sizes and longer follow-up are required to better understand the value of ICIs as neoadjuvant treatments. [Table: see text]

Background The association between proximity to oil refineries and cancer rate is largely unknown. We sought to compare the rate of cancer (bladder, breast, colon, lung, lymphoma, and prostate) according to proximity to an oil refinery in Texas. Methods A total of 6 302 265 persons aged 20 years or older resided within 30 miles of an oil refinery from 2010 to 2014. We used multilevel zero-inflated Poisson regression models to examine the association between proximity to an oil refinery and cancer rate. Results We observed that proximity to an oil refinery was associated with a statistically significantly increased risk of incident cancer diagnosis across all cancer types. For example, persons residing within 0-10 (risk ratio [RR] = 1.13, 95% confidence interval [CI] = 1.07 to 1.19) and 11-20 (RR = 1.05, 95% CI = 1.00 to 1.11) miles were statistically significantly more likely to be diagnosed with lymphoma than individuals who lived within 21-30 miles of an oil refinery. We also observed differences in stage of cancer at diagnosis according to proximity to an oil refinery. Moreover, persons residing within 0-10 miles were more likely to be diagnosed with distant metastasis and/or systemic disease than people residing 21-30 miles from an oil refinery. The greatest risk of distant disease was observed in patients diagnosed with bladder cancer living within 0-10 vs 21-30 miles (RR = 1.30, 95% CI = 1.02 to 1.65), respectively. Conclusions Proximity to an oil refinery was associated with an increased risk of multiple cancer types. We also observed statistically significantly increased risk of regional and distant/metastatic disease according to proximity to an oil refinery.

e17031 Background: Management of high-risk non-muscle invasive bladder cancer (HR NMIBC) represents a clinical challenge due to high failure rates despite prior bacillus Calmette-Guérin (BCG) therapy. We describe real-world patient characteristics, long-term outcomes, as well as the economic burden in the HR NMIBC population. Methods: We identified a random sample of 412 HR NMIBC patients who received ≥ 1 dose of BCG within Veterans Affairs (VA) centers across the United States from January 1, 2000, to December 31, 2016. HR NMIBC was defined as high-grade Ta (TaHG), T1, and/or carcinoma-in-situ (CIS). We analyzed the number of BCG instillations received, as well as used the Kaplan-Meier method to estimate event-free survival for cystectomy and bladder cancer-specific death. All-cause expenditures were summarized as medians with corresponding interquartile ranges (IQR) and adjusted to 2019 USD. Results: The median (IQR) age at diagnosis was 67 years (61-74), with most patients being white (84%) and male (81%). At HR NMIBC diagnosis, 69 (17%) patients had CIS +/- T1 or TaHG, and 341 (83%) had TaHG or T1, no CIS. The vast majority of patients [n = 363, (90%)] received six BCG instillations (range: 1-7) within 365 days of the first dose. The total follow-up was 2,694 person-years. From BCG initiation to end of follow-up, the median all-cause expenditures per patient were $358,593 (257,699 – 652,853). Conclusions: In this equal access setting, the vast majority of HR NMIBC patients received 6 instillations of BCG within 1 year, although the interval over which the instillations were given varied among patients. Patients with CIS appeared to have a worse prognosis, as 24% underwent cystectomy, and 13% died of bladder cancer at 10 years of follow-up. These findings also highlight the considerable economic burden of HR NMIBC. [Table: see text]

6576 Background: Only one out of five muscle-invasive bladder cancer patients receive radical cystectomy, a guideline-recommended treatment. Prior studies evaluated patient characteristics associated with radical cystectomy use. We aimed to determine bladder cancer diagnosing physician and hospital characteristics associated with the use of radical cystectomy. Methods: This cohort study used linked SEER-Medicare Data from 2002 to 2011. We included older adults (age>65 years) diagnosed with muscle-invasive bladder cancer. For each patient, a urologist who performed transurethral resection of bladder tumor was assigned as a diagnosing physician. The diagnosing physician was assigned to one hospital based on where he/she performed more than half of all urologic surgeries. Two-level hierarchical model (patients nested within hospitals) were constructed to determine the association of patient, physician and hospital characteristics with radical cystectomy use. Results: A total of 7,097 patients were diagnosed by 4601 physicians who were affiliated with 822 hospitals. Overall, the radical cystectomy utilization rate was 26.5%. Only 4.8% of the variation in radical cystectomy was attributed to the hospital level. In the two-level hierarchical model, patients diagnosed by female physicians were more likely to undergo radical cystectomy (32.8% vs. 25.8%; OR=1.63, 95% CI=1.31-2.02). Higher radical cystectomy volume by diagnosing physicians and hospitals increased the radical cystectomy use (Table). Diagnosing physician characteristics (age, years in practice, employment status), and hospital characteristics (teaching states, location, type of hospital) were not associated with radical cystectomy use. Patient characteristics such as age, male, higher comorbidity burden were associated with lower likelihood of radical cystectomy use. Conclusions: Physician and hospital factors do not largely contribute to the receipt of radical cystectomy. Radical cystectomy volume by diagnosing physicians and hospital drives radical cystectomy use.[Table: see text]

4538 Background: Exposure to aromatic amines is a risk factor for bladder cancer. Incidence rates according to proximity to oil refineries are largely unknown. We sought to determine proximity of oil refineries and bladder cancer incidence in the State of Texas which is home to the largest number of oil refineries in the United States. Methods: We used the Texas Cancer Registry database to identify patients diagnosed with bladder cancer from January 1, 2001 to December 31, 2014. The U.S. census data from 2010 was used to ascertain overall population size, age and sex distributions. Heat maps of the 28 active oil refineries in Texas were developed. Incidence of bladder cancer were compared according to proximity ( < 10 vs. ≥ 10 miles) to an oil refinery. Risk ratios were adjusted using a Poisson regression model. Results: A total of 45,517 incident bladder cancer cases were identified of which 5,501 cases were within 10 miles of an oil refinery. In adjusted analyses, bladder cancer risk was significantly greater among males vs. females (Relative Risk (RR) 3.41, 95% Confidence Interval (CI), 3.33-3.50), and greater among people living within 10 miles from an oil refinery than those living outside a 10-mile radius from an oil refinery (RR 1.19, 95% CI, 1.08-1.31). Conclusions: People living within 10 miles from oil refineries were at greater risk for bladder cancer. Further research into exposure to oil refineries and bladder cancer incidence is warranted.

e16029 Background: Radical cystectomy is the guideline-recommended treatment for muscle-invasive bladder cancer; however, use of trimodal therapy, which utilizes a combination of surgery, radiation, and chemotherapy, has increased in recent years with conflicting survival outcomes. Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, a total of 2,963 patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002 to December 31, 2011 were analyzed. Conventional regression, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to compare radical cystectomy and trimodal therapy for overall and cancer-specific survival, and cost. Results: Patients who underwent TMT had significantly decreased overall (conventional regression: Hazard Ratio (HR) 1.54, 95% Confidence Interval (CI), 1.39-1.71; PSM: HR 1.49, 95% CI 1.31-1.69; IPTW: HR 1.54, 95% CI 1.39-1.71) and cancer-specific (conventional regression: HR 1.51, 95% CI 1.40-1.63; PSM: HR 1.55, 95% CI 1.32-1.83; IPTW: HR 1.51, 95% CI 1.40-1.63) survival. Median total costs were significantly higher with trimodal therapy than with radical cystectomy at 6-month ($171,401 vs. $99,890, p < 0.001). Conclusions: Using population-based data and different analytic methods to control for imbalance between study groups, we found that trimodal therapy was associated with decreased overall and cancer-specific survival at increased costs compared to radical cystectomy.

373 Background: Treatment guidelines for muscle-invasive bladder cancer recommend radical cystectomy. However, use of trimodal therapy has increased in recent years with conflicting survival outcomes. The aim of this study was to compare radical cystectomy and trimodal therapy in terms of survival outcomes and cost of treatment according to varying statistical methodology in order to interpret findings using observational data. Methods: Patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002-December 31, 2011 were included from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Outcomes included cancer-specific survival, overall survival, and 6-month costs. Cox proportional hazards regression, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to control for baseline differences between patients undergoing radical cystectomy vs. trimodal therapy, and to determine predictors for overall and cancer-specific survival. Results: A total of 2,963 patients were included: 728 (24.6%) who underwent trimodal therapy were compared to 2,235 (75.4%) who underwent radical cystectomy. In all adjusted analyses, patients who underwent trimodal therapy had significantly decreased cancer-specific survival (Cox regression: Hazard Ratio (HR) 1.51, 95% Confidence Interval (CI) 1.40-1.63; PSM: HR 1.55, 95% CI 1.32-1.83; IPTW: HR 1.51, 95% CI 1.40-1.63) and overall survival (Cox regression: HR 1.54, 95% CI 1.39-1.71; PSM: HR 1.49, 95% CI 1.31-1.69; IPTW: HR 1.54, 95% CI 1.39-1.71). However, median total costs over six months were significantly higher with trimodal therapy than radical cystectomy ($171,401 vs. $99,890, p

e16021 Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days. The objective of this study is to compare the one-year costs associated with trimodal therapy versus radical cystectomy, accounting for survival and intensity effects on total costs. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Data analysis was performed from March 5, 2018 through December 4, 2018. A total of 2,963 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2011. Total Medicare costs within one year of diagnosis following radical cystectomy versus trimodal therapy were compared using inverse probability of treatment-weighted (IPTW) propensity score models, which included a two-part estimator to account for intrinsic selection bias. Results: Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83,754 vs. $68,692; median difference $11,805, 95% CI $7,745 to $15,864), 180 days ($187,162 vs. $109,078; median difference $62,370, 95% CI $55,581 to $69,160), and 365 days ($289,142 vs. $148,757; median difference $109,027, 95% CI $98,692 to $119,363), respectively. Outpatient care, radiology, medication expenses and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On IPTW-adjusted analyses, patients undergoing trimodal therapy had $129,854 (95% CI $115,793-$145,299) higher costs compared with radical cystectomy one year after diagnosis. Conclusions: Compared to radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. Extrapolating cost figures resulted in nationwide excess spending of $444 million for trimodal therapy compared with radical cystectomy for patients diagnosed in 2017.

421 Background: Radical cystectomy is the guideline-recommended treatment for muscle-invasive bladder cancer. Recently there has been a resurgence in trimodal therapy with limited data on comparative outcomes, and especially attributable costs. Methods: A total of 3,200 patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002- December 31, 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data were analyzed. Cox regression analysis and propensity score matching methods were used to determine predictors for overall and cancer-specific survival. Results: A total of 3,200 patients met inclusion criteria. After propensity score matching, 687 patients underwent trimodal therapy and 687 patients underwent radical cystectomy. Patients who underwent trimodal therapy had significantly decreased overall (Hazard Ratio (HR) 1.49, 95% Confidence Interval (CI), 1.31-1.69, p < 0.001) and cancer-specific (HR 1.55, 95% CI 1.32-1.83, p < 0.001) survival, respectively. While there was no difference in costs at 30 days, median total costs were significantly higher with trimodal therapy than radical cystectomy at 90-d ($63,355 vs. $73,420, p < 0.001) and 180-d ($98,005 vs. $164,720, p < 0.001), respectively. Extrapolating these figures to the total US population results in excess spending of $179 million for trimodal therapy compared to less costly radical cystectomy for patients diagnosed in 2011. Conclusions: Trimodal therapy was associated with significantly decreased overall and cancer-specific survival resulting in excess national spending of $179 million in 2011 compared with radical cystectomy. These findings have important health policy implications regarding appropriate use of high-value based care among patients who are candidates for either treatment.

Purpose This study compares late effects of treatment on physical well-being and utilization of health care resources between ovarian germ cell tumor (OGCT) survivors and age/race/education-matched controls. Patients and Methods Eligible patients had OGCT treated with surgery and chemotherapy and were disease-free for at least 2 years at time of enrollment. The matched control group was selected from acquaintances recommended by survivors. Symptoms and function were measured using previously validated scales. Health care utilization was assessed by questions regarding health insurance coverage and health services utilization. Results One hundred thirty-two survivors and 137 controls completed the study. Survivors were significantly more likely to report a diagnosis of hypertension (17% v 8%, P = .02), and marginally hypercholesterolemia (9.8% v 4.4%, P = .09), and hearing loss (5.3% v 1.5%, P = .09) compared with controls. There were no significant differences in the rates of self-reported arthritis, heart, pulmonary or kidney disease, diabetes, non-OGCT malignancies, anxiety, hearing loss, or eating disorders between groups. Among chronic functional problems, numbness, tinnitus, nausea elicited by reminders of chemotherapy (v general nausea triggers for controls), and Raynaud's symptoms were reported more frequently by survivors. Patients who received vincristine, dactinomycin, and cyclophosphamide in addition to cisplatin therapy had increased functional complaints, particularly numbness and nausea. Health care utilization was similar, but 15.9% of survivors reported being denied health insurance versus 4.4% of controls (P < .001). Conclusion Although a few sequelae of treatment persist, in general, OGCT survivors enjoy a healthy life comparable to that of controls.

Purpose Initial cisplatin (CIS) combination chemotherapy will cure 70% of patients with disseminated testicular cancer. This phase II clinical trial evaluated the combination of CIS plus epirubicin (CIS-EPI) in patients with metastatic germ cell tumors (GCT) not amenable to cure with standard salvage therapy. Patients and Methods Between March 2001 and August 2005, 30 patients with GCT, who had received at least one previous CIS-based regimen, were enrolled. All patients were males, with median age 36 (range, 24 to 45 years). Twenty-one patients (70%) had experienced late relapses (> 2 years). Patients received EPI 90 mg/m2 on day 1 and CIS 20 mg/m2 on days 1 to 5 every 3 weeks for maximum of four cycles. Results Nineteen (63%) of 30 patients received all four cycles. Toxicity was primarily hematologic: grade 3/4 neutropenia, four patients (one neutropenic fever); two patients had grade 3 thrombocytopenia, and five patients had grade 3/4 anemia. Nonhematologic toxicity was grade 3 acute renal failure in two patients; grade 3 electrolyte wasting in two patients; grade 3 nausea/vomiting in eight patients; grade 3 elevation of aminotransferases in one patient; and grade 3 diarrhea in one patient. There were no occurrences of severe mucositis, cardiotoxicity, or treatment-related deaths. Nine patients achieved a complete remission; seven of these patients remain without evidence of disease at 25+, 27+, 29+, 44+, 45+, 46+, and 48+ months. One patient remains alive with stable pulmonary nodules at 28+ months. Conclusion CIS-EPI is an active regimen in metastatic GCT, with an acceptable toxicity profile. This regimen offers potential for long-term disease-free survival in this population.

368 Background: This study examined utilization patterns and predictors for use of positron emission tomography-computed tomography (PET/CT), magnetic resonance imaging (MRI), and computed tomography (CT) among Medicare beneficiaries diagnosed with bladder cancer. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data for 36,855 patients aged 60-90 years diagnosed with bladder cancer from 2004 to 2011. The Cochran-Armitage test for trend was used to determine whether significant changes in the proportion of patients receiving advanced imaging after cancer diagnosis occurred during the time interval; trends in the usage of the imaging modality types were assessed. Multivariable logistic regression modeling was conducted to analyze potential demographic and clinical predictors associated with receipt of advanced imaging. The costs of imaging were measured using Medicare payments. Results: While the overall trend of imaging use remained essentially unchanged over the study period, there was a significant decrease in the proportion of patients who received conventional imaging modalities (MRI and CT; P < .05) and a significant increase in the proportion of patients receiving the more advanced imaging modality (PET/CT; P < .0001). On multivariable analysis, receipt of PET/CT was significantly higher in female patients, Non-Hispanics, residents in West Census region, patients with higher grade tumors, those diagnosed with advanced stage disease, hydronephrosis, and those that received radical cystectomy and chemotherapy. In the cost analysis, the estimated national excess medical spending for advanced imaging was $6.1 million. Conclusions: The sharp increase of advanced imaging (PET/CT) and substantial costs associated with this rapid adoption as we have documented suggests that further efforts should be made to evaluate the clinical and economic benefits of PET/CT imaging and to elucidate its appropriateness of use among bladder cancer patients.

360 Background: Radical cystectomy is an underutilized option for those with refractory non-muscle invasive and muscle-invasive bladder cancer, however, use of radical cystectomy may differ according to gender. We wanted to discern receipt and timing of radical cystectomy as well as survival outcomes according to gender. Methods: A total of 49,974 patients aged 66 years or older diagnosed with clinical stage I-IV bladder cancer from January 1, 2002 to December 31, 2011 using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. We used univariate and multivariable regression analyses to identify factors predicting the use of radical cystectomy. Cox proportional hazards models were used to analyze survival outcomes. Generalized linear models were performed to determine association between gender and delayed radical cystectomy. Results: A total of 49,974 patients were diagnosed with stage I to IV bladder cancer. 36,959 (74%) were male patients. Women were older, non-Caucasian race/ethnicity, with increased comorbidities and presented with more advanced disease (all p

14 Background: National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). Methods: A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs. Results: Patients with proximity to ≥ 2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p < 0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p = 0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. Conclusions: Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers.

37 Background: To compare overall survival of patients who underwent radical prostatectomy or radiotherapy versus non-cancer controls in order to discern if there is a survival advantage according to prostate cancer treatment. Methods: A matched cohort study was performedusingthe Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We identified 34,473 patients age 66 to 75 years without significant comorbidity from who were diagnosed with localized prostate cancer treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a non-cancer control cohort. We compared the rates of all-cause mortality that occurred within the study period. We used Cox Proportional Hazards Regression analysis to identify determinants associated with overall survival. Results: Of the total 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy and 12,733 (37%) received surgery. When compared to the non-cancer control, there was no significant difference between the prostate cancer cohort and the non-cancer control group with exception of race/ethnicity (p < 0.001). There was improved survival in patients treated with surgery (hazard ratio [HR], 0.35; 95% CI, 0.32-0.38) as well as with radiotherapy (HR, 0.72; 95% CI, 0.68-0.75) when compared to non-cancer controls. There was significantly improved overall survival among both treatment groups with most benefit observed among patients who underwent surgery ( log rank p < 0.001). Conclusions: Using population based data, treatment with either surgery or radiotherapy demonstrated improved overall survival when compared to a cohort of matched non-cancer controls. Treatment with surgery resulted in longer overall survival compared to those receiving radiation therapy. These results suggest inherent selection-bias due to unmeasured confounding variables when using cancer registry data.

422 Background: The passage of the Affordable Care Act (ACA) in 2010 aimed to improve access for uninsured patients to private health insurance. Yet, the impact of the ACA on the number of privately insured young patients and on the timeliness of medical care for serious medical conditions, remain unclear. Thus, we sought to ascertain changes in insurance status and evaluate timeliness of post-orchiectomy definitive therapy for young men diagnosed with testicular cancer following passage of the ACA. Methods: From the National Cancer Database, we identified all patients 18 – 50 years of age diagnosed with stages I – III testicular cancer from 2007 to 2013. Patients were divided into groups at the time of diagnosis; 2007 – 2009 (pre-ACA) and 2011 to 2013 (post-ACA). Only patients who had undergone radical orchiectomy and had a reported insurance status were included in analysis. The primary outcomes were insurance type at diagnosis and time to treatment of secondary therapy following orchiectomy (systemic chemotherapy, radiation therapy, or surgery {Retroperitoneal lymph node dissection; RPLND}). Results: Overall, 17,945 patients were included in analysis with 53.5% diagnosed with pure seminoma and 46.5% diagnosed with nonseminomatous germ cell tumor (NSGCT). In comparing pre- and post-ACA cohorts, the percentage of patients with private health insurance decreased following the passage of the ACA (74.1% vs. 71.2%; p < 0.01). Similarly, the percentage of patients without any insurance increased between the two time frames (12.7 % vs. 13.4%; p < 0.01). More patients presented with clinical stage II and III disease following the passage of the ACA (28.9% vs. 31.9%; p < 0.01). Compared to patients without health insurance, privately insured patients received more timely secondary definitively therapy with radiation therapy (49.9 vs. 60.9 days, p < 0.01) and chemotherapy (41.5 vs. 45.7 days, p < 0.01) but no difference in the time to RPLND (18.8 vs. 16.7 days, p = 0.70). Conclusions: The impact of the ACA on patients with testicular cancer shows minimal worsening in the number of privately insured young men and increasing rates of advanced testis cancer. This was not in agreement with our hypothesis and suggests the ACA is not benefiting young men with this malignancy.

PURPOSE We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.

Between 1984 and 1989, 159 patients presenting with advanced germ cell cancer were entered on a randomized clinical trial comparing the efficacy and toxicity of etoposide and bleomycin and either standard-dose cisplatin (20 mg/m2 daily for 5 days) or high-dose cisplatin (40 mg/m2 daily for 5 days). Of the 159 patients, 153 were assessable for toxicity and response. As expected, patients receiving the high-dose cisplatin regimen experienced significantly more neurotoxicity, ototoxicity, nausea and vomiting, and myelo-suppression. Four patients (3%) died related to therapy. Despite the toxicity encountered, dose intensity was maintained. Overall, 84% of patients in the high-dose arm received 80% or more of the projected dose of cisplatin, etoposide, and bleomycin; and 90% of patients on the standard-dose arm received 80% or more of the projected dose. Of the 76 eligible patients randomized to receive the high-dose cisplatin regimen, 52 (68%) became disease-free with chemotherapy alone or with subsequent resection of residual teratoma or cancer. Of the 77 patients randomized to the standard-dose arm, 56 (73%) became disease-free with chemotherapy alone or with surgery. Median follow-up is now 24 months. Eleven patients (three high-dose and eight standard-dose) relapsed from disease-free status. Overall, 74% of patients receiving the high-dose cisplatin regimen are alive, and 63% are continuously free of disease. Of the patients receiving the standard-dose cisplatin regimen, 74% are alive, and 61% are continuously free of disease. This randomized prospective trial in advanced germ cell cancer achieved dose intensity of the most active single agent in this disease. This dose intensity did not translate into an improved survival or cure. We conclude that dose escalation of cisplatin beyond standard doses results in excess toxicity with no accompanying therapeutic benefit.

378 Background: Fluorescence cystoscopy (also known as blue-light cystoscopy (BL)) is an adjunct to white light cystoscopy (WL) and aids in visualization of tumors that may be missed with WL as well as allow more complete resection of tumors. Herein we present the impact of BL on subsequent patient management in a real world setting. Methods: A total of 116 consecutive patients who underwent simultaneous BL and WL from January 2013 through December 2014 were included in the study. Pathology and operative reports were reviewed to determine the grade and stage of the tumors and whether they were viewed under BL or WL. Results: Of the 116 patients, a total of 161 biopsies and/or transurethral resected specimens were analyzed. Of these, 46 (28.6%) lesions were seen only with BL, none were seen only with white light, 109 (67.7%) were seen with both, and 7 (4.4%) were identified via random biopsies. Of the 46 lesions seen only on BL, 17 (37%) were positive for cancer, while, of the 109 lesions seen with WL and BL, 84 (77%) were positive. Of the 17 (37%) true positive tumors seen only on BL, the stage and grades were; 5 (29.4%) low-grade Ta, 2 (11.8%) high-grade Ta, 1 (5.9%) high-grade T1, and 9 (52.9%) CIS. There were no instances of a tumor being found on WL that was not also visualized with BL. In this patient cohort, the false positive rates were 23% and 63% for WL and BL, respectively. The false negative rates were 0.9% and 2.1% for WL and BL, respectively. For the 46 (28.6%) lesions that were visible by BL, WL cystoscopy was not able to visualize 10 (21.7%) tumors visualized by BL. In addition, there was one patient who had multiple lesions sent for pathology by BL and WL, and the lesions identified by BL were of higher stage than the lesions visualized by WL. Conclusions: BL identified additional tumors that would have been missed with WL. Moreover, in patients who had tumors visualized only with BL, 11 (26.8%) were high-grade, including one (2.4%) patient with T1 tumor and 8 (19.5%) with CIS. Thus, BL identified a number of high-risk tumors, which had a significant impact on the subsequent management of patients with bladder cancer.

11 Background: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. Self-referral for radiation therapy according prostate cancer risk and cost of care is not known. We evaluated how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referring urologic practice (SRP) compared to a traditional urologic practice. Methods: 17,982 men 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. Disease was classified as favorable if low-grade and clinical T1 or T2. The diagnosing urologist was classified as being affiliated with a SRP if their practice owned a linear accelerator. Multilevel logistic regression models evaluated the odds of receiving a specific type of treatment adjusted for diagnosis year, age, comorbidities, race/ethnicity, income, education, clinical tumor stage, and tumor grade. Cost of care was calculated from Medicare expenditures within 12 months of diagnosis. Results: Diagnosis in a SRP increased from 2.2% of prostate cancers in 2004 to 24.5% in 2009 (p< 0.001). Men diagnosed in SRPs were more likely to receive upfront treatment (vs. watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs. 89%; AOR 1.61, p

416 Background: One of the criticisms of blue-light cystoscopy (BL) is the relatively high rate of false positive biopsies when used in the real world setting. There is no consensus on which patient factors, if any, might be contributing to this high false positive rate. The purpose of this study is to determine whether having a cystoscopy, TURBT or BCG treatment recently resulted in higher rates of false positive blue-light (BL) biopsies. Methods: We performed an IRB-approved retrospective study looking at a total of 116 consecutive patients who underwent simultaneous BL and WL between January 2013 to December 2014. Pathology and operative reports were reviewed to determine the grade and stage of the tumors. Clinical notes were utilized to determine how recently they had a cystoscopy, TURBT, and BCG treatment. The false positive rates of both BL and WL were calculated, and Fisher’s exact test was utilized to determine if the time from the patients’ most recent bladder manipulation or BCG treatment had a significant effect on the false positive BL rate. Results: Of the 46 (28.6%) BL positive biopsies, 29 (63.0%) were false positives. When stratified by potential causes of false positive for BL we found the following: one (3.4%) had bladder manipulation within 14 days, 8 (27.6%) within 30 days, 19 (65.5%) within 60 days, and 10 (34.5%) had bladder manipulation beyond 60 days prior to the biopsy. When looking at intravesical BCG as a cause for false positive, we found prior BCG use in 18 (62%) patients of those with false positive BL compared to 12 (70.6%) patients of those with true positive BL biopsies (p = 1.0). Of the 18 patients with false positive BL biopsies who had BCG previously: 1 (5.6%) had BCG within 6 weeks, 5 (27.8%) had BCG within 12 weeks, and 13 (72.2%) had BCG greater than 12 weeks prior to biopsy. None of these associations were found to be statistically significant. Despite the high percentage of false positive lesions, it is important to note that in patients who had tumors visualized only with BL, 11 (26.8%) were high-grade, including one patient with T1 tumor and 8 with CIS. Conclusions: There was no relationship between recent bladder manipulation or BCG treatment and false positive BL biopsies.

e15505 Background: Most bladder cancer patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Tumor recurrence among NMIBC patients is common. Post-operative intravesical chemother...

302 Background: Micropapillary bladder cancer (MPBC) is an aggressive variant of urothelial carcinoma. We have previously published clinical risk stratification groups for patients with conventional urothelial carcinoma and sought to identify if these were valid in patients with this variant histology. Methods: An IRB approved review of 1910 patients in our radical cystectomy database revealed 106 patients with preoperative diagnosis of ≤cT4aN0M0 MPBC between December 1992 and January 2012 who underwent upfront radical cystectomy (RC, n = 74) or neoadjuvant chemotherapy (NAC) followed by RC (n = 32). To determine whether patients with MPBC can be risk stratified using traditional risk factors, a recursive partitioning analysis (RPA) was performed. Results: In multivariate analyses, hydronephrosis (HR=3.1; p=0.01), and extent of MPBC at transurethral resection (TUR) (HR=1.9; p=0.04) were associated with shortened OS. In the reduced model, clinical stage also achieved significance (HR=2.8; p=0.03). Results were similar for DSS: hydronephrosis (HR=2.4, p=0.03), extent of MPBC (HR=2.1, p=0.03) and clinical stage (HR=4.7, p=0.02). Using the RPA analysis, following risk groups were identified according to OS or DSS: 1) cT1 disease with no hydronephrosis; 2) cT2 or higher with no hydronephrosis; or 3) hydronephrosis (with any cT stage). These groups corresponded to a low, intermediate and high-risk groups with 5-year OS and DSS rates of 85% and 91%, 50% and 57% and 16% and 17%, (p

66 Background: There is limited evidence definingthe morbidity of radical prostatectomy (RP) with curative intent for patients with high risk prostate cancer. Multimodality treatment for men with high risk prostate cancer using neoadjuvant systemic therapy followed by surgery is being increasingly explored. Methods: We analyzed 215 consecutive patients with high risk and very high risk prostate cancer who underwent robotic or open RP with extended pelvic lymph node dissection previously untreated or received neoadjuvant systemic therapy between 2006 and 2010 at a single tertiary care academic center. Univariable and multivariable logistic regression analyses were used to identify predictors of complications. Results: Baseline characteristics were similar between patients who underwent neoadjuvant systemic therapy followed by RP versus RP alone except for PSA (PSA< or equal to 4 ng/ml: 75.4% vs. 15.5%, p

9551 Background: Ovarian germ cell tumors (OGCT) are rare tumors curable with modern surgery and chemotherapy. Late effects of therapy in survivors have not been described. This multi-site study compares the late effects of treatment on physical well being and utilization of health care resources between OGCT survivors and an age/race/education-matched control group. Methods: Eligible patients had a history of OGCT treated with surgery plus platinum-based chemotherapy on GOG protocols and were free of disease for at least 2 years at time of enrollment. The matched control group was selected from acquaintances recommended by survivors. Data were collected through mailed background questionnaires and computer-assisted telephone interviews. Physical functioning was measured using validated scales (SF36 and FACT/GOG-NTX). Health care utilization was assessed by questions regarding health insurance coverage, health services utilization and employment. Wilcoxon Rank Sum and Fisher’s exact tests were used for st...

4549 Background: We began studies with HDCE for patients (pts.) with recurrent GCTs 20 years ago. During the past decade, better supportive care and use of PBSCT allowed outpatient therapy and more rapid hematopoietic recovery between the 2 courses of HDCE. Methods: Retrospective review of 184 consecutive pts. treated with HDCE at Indiana University from 2–96 to 12–04. Late relapse (> 2 years from prior therapy) and primary mediastinal non-seminomatous germ cell tumor pts. were not offered HDCE. Cytoreduction with 0–2 courses of vinblastine + ifosfamide + cisplatin preceded HDCE. C dosage was 700 mg/M2 × 3 and E 750 mg/M2 × 3. A second course was given after hematologic recovery. Results: Toxicity was as previously described (JCO 18:3346, 2000). There were 3 drug- related mortalities. An additional 3 patients developed AML (2 fatal), and 1 glioma following CNS XRT for metastases. 11 pts. did not receive second course (8 due to progression or HDCE mortality). Median time to second course HDCE was 28 days (range 20 to 42). 116 of 184 pts. are alive and continuously (cont) NED (63%) with median followup 42 months (range 11 to 118). 113 (97%) of these are 12+ months NED. 5 additional pts. are currently NED with further therapy. Results are tabulated below. Conclusions: HDCE has a high cure rate with acceptable toxicity as salvage therapy for GCT pts. [Table: see text] [Table: see text]

In late 1974, the combination of cisplatin, vinblastine, and bleomycin (PVB) became the standard chemotherapeutic regimen for treatment of disseminated nonseminomatous germ cell testicular tumors (NSGCT) at Indiana University Hospital. A retrospective analysis of the treatment records of all patients with brain metastases from NSGCTs treated at the Indiana University Radiation Oncology Department from 1975 through 1982 was undertaken. These 22 patients were divided into four groups. Group 1 (n = 5) consisted of those patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) were referred to Indiana University after failing systemic therapy other than PVB chemotherapy. Group 3 (n = 5) consisted of those patients who after achieving a complete response with PVB developed a relapse confined to the brain. Group 4 (n = 8) consisted of those patients who were initially treated with PVB and eventually developed progressive disease and brain metastases. The survival by group is 80%, 0%, 60%, and 0%, respectively, with the overall survival for the entire group being 31.8%. All patients currently alive have a range of follow-up of 22 to 96 months from diagnosis and 12 to 83 months from whole brain irradiation (WBRT). Group 1 was treated with PVB +/- doxorubicin plus WBRT. Group 3 was treated with surgical excision, when feasible, followed by WBRT and platinum-containing chemotherapy. Group 2 and 4 were usually treated with palliative intent WBRT. The CNS is a site of sanctuary from PVB. Patients with brain metastases who may achieve a complete response should be treated with curative intent and receive aggressive WBRT (5,000 rad/25 fractions) with concomitant chemotherapy.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.

From April 1982, until February 1984, 29 patients with biopsy-proven and measurable adenocarcinoma of the pancreas were treated with ifosfamide. Ifosfamide was administered at a dose of 1.25 to 1.5 g/m2 daily for five consecutive days with courses repeated every three weeks. If no serious toxicity was noted, subsequent dosages were escalated to a maximum of 2.0 g/m2/d. In addition, N-acetylcysteine (NAC) (8 to 12 g/d) was administered (in divided daily doses days 1 through 7) as a urothelial protective agent. Nausea and vomiting occurred in the majority of the treated patients. Other toxicities noted were mild myelo-suppression, CNS toxicity, and one case of acute renal failure. One complete response (CR) and five partial responses (PR) were observed in 27 evaluable patients (CRs and PRs = 22%). Ifosfamide has definite activity against pancreatic adenocarcinoma. Doses greater than 1.2 g/m2 for days 1 through 5 can be administered without significant toxicity in the majority of patients. Further trials with ifosfamide alone and/or with other agents are warranted.

Thirty-six patients with advanced seminoma treated with cisplatin combination chemotherapy were evaluated to assess the significance of postchemotherapy residual radiographic mass. All patients had a minimum follow-up of 2 years. Of the 36 patients 21 had an evaluable residual radiographic mass after completion of chemotherapy. Twelve of these patients had a less than 3 cm maximal transverse diameter residual mass, and nine had a greater than 3 cm persistent mass postchemotherapy. Only three of these 21 patients underwent postchemotherapy retroperitoneal lymph node dissection, and the histopathology revealed only necrotic fibrous tissue. The remaining patients were followed by close observation including repeat abdominal computed tomography (CT) every 3 months the first year and every 6 months the second year (or until normal); further therapeutic intervention was given only on evidence of progressive disease. Nineteen of these 21 patients have no evidence of disease, including eight of nine with greater than 3 cm persistent radiographic abnormality. The optimal management for advanced seminoma patients with a persistent radiographic mass postchemotherapy remains unresolved. However, based on this small series, we feel that observation is a viable option, reserving radiotherapy or chemotherapy for those patients who subsequently develop progressive disease.

Patients with testicular cancer who have disseminated disease at presentation do not always undergo orchiectomy for diagnosis of staging before initiation of chemotherapy. Between October 1978 and November 1982 orchiectomy was performed following cisplatin combination chemotherapy in 20 patients with disseminated germ cell tumors. There were three patients with residual carcinoma in the removed testis and six patients with teratoma. Therefore, in patients with evidence of a primary testicular neoplasm that was not resected initially, orchiectomy should be performed after chemotherapy. Furthermore, the testis may be a sanctuary site for germ cell malignancies during systemic treatment.